臨床泌尿器科66巻12号

2012年11月発行

綜説

去勢抵抗性前立腺癌（CRPC）に対する新たな治療体系

著者： 住友誠¹

所属機関： ¹愛知医科大学医学部泌尿器科学講座

ページ範囲：P.907 - P.917

要旨　去勢抵抗性前立腺癌（castration-resistant prostate cancer：CRPC）は，去勢抵抗性ではあるがAR依存性である癌（狭義のCRPC）と去勢抵抗性かつAR非依存性（HRPC）に分類されるべきである。狭義のCRPCとHRPCを臨床的に厳密に区別することは非常に難しい。2010年以降の新規薬剤の登場により，再燃前立腺癌に対する治療体系は変革時代を迎えた。つまり，いままでdocetaxel一辺倒であったCRPC治療に新たな治療戦略が加えられたのである。しかも，これらの薬剤は，狭義のCRPCとHRPCに対する個別化治療戦略という意味では非常に魅力的な内容を含んでいる。本稿ではCRPCに対する新たな治療戦略を企てるうえでも，「内分泌療法」と「化学療法」という機序のまったく異なる薬剤の選択基準について概説する。

参考文献

1）Sumitomo M, Shen R, Walburg M, et al：Neutral endopeptidase inhibits prostate cancer cell migration by blocking focal adhesion kinase signaling. J Clin Invest 106：1399, 2000

2）Hellerstedt BA and Pienta KJ：The current state of hormonal therapy for prostate cancer. CA Cancer J Clin 52：154, 2002

3）Attard G, Sarker D, Reid A, et al：Improving the outcome of patients with castration-resistant prostate cancer through rational drug development. Br J Cancer 95：767, 2006

4）Schroder FH：Progress in understanding androgen-independent prostate cancer（AIPC）：a review of potential endocrine-mediated mechanisms. Eur Urol 53：1129, 2008

5）Mottet N, Bellmunt J, Bolla M, et al：EAU guidelines on prostate cancer. Part Ⅱ：treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 59：572, 2011

6）National Comprehensive Cancer Network：NCCN clinical guidelines in oncology：prostate Cancer, Version 3, NCCN, Fort Washington, 2012

7）Tannock IF, de Wit R, Berry WR, et al：Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351：1502, 2004

8）Petrylak DP, Tangen CM, Hussain MH, et al：Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351：1513, 2004

9）Scher HI, Steineck G and Kelly WK：Hormone-refractory（D3）prostate cancer：refining the concept. Urology 46：142, 1995

10）de Bono JS, Logothetis CJ, Molina A, et al：Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364：1995, 2011

11）Ryan CJ, Smith MR, de Bono JS, et al：Interim analysis（IA）results of COU-AA-302, a randomized, phase Ⅲ study of abiraterone acetate（AA）in chemotherapy-naive patients（pts）with metastatic castration-resistant prostate cancer（mCRPC）. J Clin Oncol 30, 2012（suppl；abstr LBA4518 of 2012 ASCO meeting）, 2012

12）de Bono JS, Oudard S, Ozguroglu M, et al：Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment：a randomised open-label trial. Lancet 376：1147, 2010

13）Kantoff PW, Higano CS, Shore ND, et al：Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363：411, 2010

14）Scher HI, Fizazi K, Saad F, et al：Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med, 2012 Aug 15.［Epub ahead of print］

15）Tran C, Ouk S, Clegg NJ, et al：Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324：787, 2009

16）Dreicer R, Petrylak D, Agus D, et al：Phase Ⅰ/Ⅱ study of bortezomib plus docetaxel in patients with advanced androgen-independent prostate cancer. Clin Cancer Res 13：1208, 2007

17）Sartor AO and Fitzpatrick JM：Urologists and oncologists：adapting to a new treatment paradigm in castration-resistant prostate cancer（CRPC）. BJU Int 110：328, 2012

18）Shore ND：Chemotherapy for prostate cancer：when should a urologist refer a patient to a medical oncologist? Prostate Cancer Prostatic Dis, 2012［Epub ahead of print］

19）Ryan CJ, Li J, Kheoh T, et al：Abstract LB-434：Baseline serum adrenal androgens are prognostic and predictive of overall survival（OS）in patients（pts）with metastatic castrate-resistant prostate cancer（mCRPC）：results of the COU-AA-301 phase 3 randomized trial. AACR 103rd Annual Meeting 2012, 2012

20）Efstathiou E, Titus M, Tsavachidou D, et al：Effects of abiraterone acetate on androgen signaling in castrate-resistant prostate cancer in bone. J Clin Oncol 30：637, 2012

21）Sumitomo M, Ohba M, Asakuma J, et al：Protein kinase Cdelta amplifies ceramide formation via mitochondrial signaling in prostate cancer cells. J Clin Invest 109：827, 2002

22）Mezynski J, Pezaro C, Bianchini D, et al：Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone：clinical evidence for cross-resistance? Ann Oncol, 2012

23）de Bono JS, Scher HI, Montgomery RB, et al：Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14：6302, 2008

24）Scher HI, Jia X, de Bono JS, et al：Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer：a reanalysis of IMMC38 trial data. Lancet Oncol 10：233, 2009

25）Danila DC, Pantel K, Fleisher M, et al：Circulating tumors cells as biomarkers：progress toward biomarker qualification. Cancer J 17：438, 2012

26）Oh WK and Kantoff PW：Docetaxel（Taxotere）-based chemotherapy for hormone-refractory and locally advanced prostate cancer. Semin Oncol 26：49, 1999

27）Lin AM, Ryan CJ and Small EJ：Intermittent chemotherapy for metastatic hormone refractory prostate cancer. Crit Rev Oncol Hematol 61：243, 2007

28）Mountzios I, Bournakis E, Efstathiou E, et al：Intermittent docetaxel chemotherapy in patients with castrate-resistant prostate cancer. Urology 77：682, 2011

29）Oh WK：Secondary hormonal therapies in the treatment of prostate cancer. Urology 60：87, 2002